DESCRIPTION (applicant?s abstract): In the absence of environmental time cues, animals continue to exhibit daily cycles in behavior and physiology with a period of approximately 24 h. In mammals, these rhythms are endogenously generated by bilaterally symmetric nuclei situated above the optic chiasm, the suprachiasmatic nuclei (SCN). A direct retinohypothalamic tract (RHT) from retinal ganglion cells to the SCN is responsible for transmitting light information from the retina to the circadian pacemaker to allow animals to entrain (synchronize) these endogenous rhythms with the environmental light:dark cycle. An important question is what neurotransmitter(s) are involved in the signal transduction pathway from the retina to the SCN. The goal of the present proposal is to investigate the role of nitric oxide in photic entrainment and circadian organization. The present proposal has three specific aims: Specific Aim I: To determine the role of NO in the SCN in photic entrainment. Specific Aim II: To understand the neuroanatomical relationship of NO-positive cells to other known cell types / components of the SCN. Specific Aim III: To clarify the role of NO as an output signal, or as an intra-SCN coordination signal, to modulate circadian locomotor rhythms.